NADPH REDUCTASES AND POLYOL PATHWAY IN OCULAR COMPLICATIONS

喂食半乳糖饮食的狗出现视网膜毛细血管变化， 类似于人类糖尿病视网膜病变。这种动物模型不发育 仅早期毛细血管改变，如微动脉瘤和各种大小 而且是增殖性视网膜病变的晚期， 新血管长入玻璃体的变化。这表明 就像人类的视网膜病一样， 是半乳糖喂养狗视网膜变化的基础。到 了解毛细血管阻塞的机制， 这些视网膜病变，我们的研究一直集中在 视网膜毛细血管细胞和白细胞的相互作用。 狗放在30%半乳糖饮食显示淋巴细胞和 中性粒细胞功能障碍凝集素诱导的胚泡形成 从半乳糖喂养的狗中分离的淋巴细胞显著降低 与非半乳糖血症对照犬相比。虽然许多中性粒细胞 趋化性等功能在正常范围内，诱导 半乳糖喂养的狗中NADPH氧化酶减少。犬中性粒细胞 通过各种刺激剂如TNF-α、PMA和 放线菌酮。这三种刺激剂诱导的细胞凋亡是 在半乳糖喂养的狗中显著抑制。尽管表面 抑制细胞凋亡，从半乳糖喂养的 狗表现出显着增加的相互作用与视网膜 毛细血管内皮细胞由于感染率较高， 发生在糖尿病患者和各种反应 糖尿病患者的炎症往往比 在非糖尿病患者中，活化的中性粒细胞的相互作用增加， 启动或加速毛细血管阻塞， 糖尿病视网膜病变

Dogs fed galactose diet develop retinal capillary changes that are similar to human diabetic retinopathy. This animal model develops not only early capillary changes such as microaneurysms and various sizes of retinal hemorrhages but also the advanced stage of proliferative changes where new vessels grow into vitreous body. This indicates that, like human retinopathy, the occlusion of retinal capillaries underlie the development of retinal changes in galactose-fed dogs. To understand the mechanism of capillary occlusion, which initiates these retinal lesions, our research has been focussed on the interaction of retinal capillary cells and leukocytes. Dogs placed on 30% galactose diet displayed both lymphocyte and neutrophil dysfunction. Blastformation induced by lectins of lymphocytes isolated from galactose-fed dogs was significantly lower than that of non-galactosemic control dogs. Although many neutrophil functions such as chemotaxis were in the normal range, induction of NADPH oxidase was decreased in galactose-fed dogs. Dog neutrophils undergo apoptosis by various stimulants such as TNF-alpha, PMA and cycloheximide. Apoptosis induced by these three stimulants was significantly suppressed in galactose-fed dogs. Despite the apparent suppression of apoptosis, neutrophils isolated from galactose-fed dogs demonstrated a dramatically increased interaction with retinal capillary endothelial cells. Since a higher incidence of infection occurs in patients with diabetes and the reaction to various inflammations tends to be more severe in diabetics than non-diabetics, the increased interaction of activated neutrophils may either initiate or accelerate capillary occlusion observed in diabetic retinopathy.